Prospective randomized trial of ACUSEAL (Gore-Tex) versus Hemashield-Finesse patching during carotid endarterectomy: Early results

Background/PurposeSeveral studies have reported that carotid endarterectomy (CEA) with patch angioplasty produces superior results compared with primary closure. Conventional polytetrafluoroethylene (PTFE) patching has been shown to have results comparable to autogenous vein patching; however, it requires a prolonged hemostasis time. Therefore, many surgeons use collagen-impregnated Dacron patching (Hemashield [HP]). Recently, we reported a satisfactory hemostasis time using the new hemostatic PTFE patch (ACUSEAL by Gore). This study is the first prospective randomized trial comparing the ACUSEAL patch with the HP Finesse patch.Methods200 CEAs were 1:1 randomized into two patch closure groups (ACUSEAL or Finesse). All patients underwent immediate and 1 month postoperative duplex ultrasound studies. Demographic and clinical characteristics were similar in both groups, including the mean operative diameter of the internal carotid artery and length of arteriotomy.ResultsThe overall perioperative ipsilateral stroke rate was 2% (2% ACUSEAL, 2% Finesse; P = 1.0). The perioperative ipsilateral TIA rates were 0% for the ACUSEAL and 2% for the Finesse patch (P = .5). The combined perioperative neurological event (TIA + stroke) rates were 2% for ACUSEAL and 4% for the Finesse (P = .68). The early ≥50% restenosis rate was 0% for ACUSEAL vs 4% for Finesse patching. Two perioperative carotid thromboses were noted with Finesse patching vs none with ACUSEAL patching (P = .50). The combined early morbidity rate (TIA, stroke, and ≥50% restenosis or thrombosis) was 2% for the ACUSEAL patch vs 8% for the Finesse patch (P = .10). The mean hemostasis time for the ACUSEAL and Finesse patches was 5.1 vs 3.7 minutes (P = .01), however, the mean operative times were similar for both groups (P = .61).ConclusionThe perioperative neurological events and overall short-term morbidity associated with CEA when using ACUSEAL or Finesse patches were similar. Both patches have short hemostasis times

NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771. Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint. Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SD \u3e 6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SD \u3e 6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Gr ≥ 3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm. Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss

ALMA 1.3 Millimeter Map of the HD 95086 System

Planets and minor bodies such as asteroids, Kuiper-belt objects and comets are integral components of a planetary system. Interactions among them leave clues about the formation process of a planetary system. The signature of such interactions is most prominent through observations of its debris disk at millimeter wavelengths where emission is dominated by the population of large grains that stay close to their parent bodies. Here we present ALMA 1.3 mm observations of HD 95086, a young early-type star that hosts a directly imaged giant planet b and a massive debris disk with both asteroid- and Kuiper-belt analogs. The location of the Kuiper-belt analog is resolved for the first time. The system can be depicted as a broad ($\Delta R/R \sim$0.84), inclined (30\arcdeg$\pm$3\arcdeg) ring with millimeter emission peaked at 200$\pm$6 au from the star. The 1.3 mm disk emission is consistent with a broad disk with sharp boundaries from 106$\pm$6 to 320$\pm$20 au with a surface density distribution described by a power law with an index of --0.5$\pm$0.2. Our deep ALMA map also reveals a bright source located near the edge of the ring, whose brightness at 1.3 mm and potential spectral energy distribution are consistent with it being a luminous star-forming galaxy at high redshift. We set constraints on the orbital properties of planet b assuming co-planarity with the observed disk.Comment: accepted for publication in A

Using a runway paradigm to assess the relative strength of rats' motivations for enrichment objects

Laboratory animals should be provided with enrichment objects in their cages; however, it is first necessary to test whether the proposed enrichment objects provide benefits that increase the animals’ welfare. The two main paradigms currently used to assess proposed enrichment objects are the choice test, which is limited to determining relative frequency of choice, and consumer demand studies, which can indicate the strength of a preference but are complex to design. Here, we propose a third methodology: a runway paradigm, which can be used to assess the strength of an animal’s motivation for enrichment objects, is simpler to use than consumer demand studies, and is faster to complete than typical choice tests. Time spent with objects in a standard choice test was used to rank several enrichment objects in order to compare with the ranking found in our runway paradigm. The rats ran significantly more times, ran faster, and interacted longer with objects with which they had previously spent the most time. It was concluded that this simple methodology is suitable for measuring rats’ motivation to reach enrichment objects. This can be used to assess the preference for different types of enrichment objects or to measure reward system processes

Systemic Sclerosis–Associated Interstitial Lung Disease: How to Incorporate Two Food and Drug Administration–Approved Therapies in Clinical Practice

Systemic sclerosis (SSc; scleroderma) has the highest individual mortality of all rheumatic diseases and interstitial lung disease (ILD) is among the leading causes of SSc-related death. Two drugs are now approved by the Food & Drug Administration (FDA) and indicated for slowing the rate of decline in pulmonary function in patients with SSc-ILD: nintedanib (a tyrosine kinase inhibitor) and tocilizumab (the first biologic agent targeting the interleukin-6 pathway in SSc). In addition, two generic drugs with cytotoxic and immunoregulatory activity, mycophenolate mofetil and cyclophosphamide, have shown comparable efficacy in a Phase II trial but are not FDA-approved for SSc-ILD. In light of the heterogeneity of the disease, the optimal therapeutic strategy in the management of patients with SSc-ILD is still to be determined. The objectives of this review are two-fold: (1) review the body of research focused on the diagnosis and treatment of SSc-ILD; and (2) propose a practical approach for diagnosis, stratification, management, and therapeutic decision-making in this clinical context. This review presents a practical classification of SSc patients in terms of disease severity (subclinical vs. clinical ILD) and associated risk of progression (low vs. high risk). The pharmacological and non-pharmacological options as first and second-line therapy, as well as potential combination approaches, are discussed in light of the recent approval of tocilizumab for SSc-ILD

Area-charge inequality for black holes

The inequality between area and charge $A\geq 4\pi Q^2$ for dynamical black holes is proved. No symmetry assumption is made and charged matter fields are included. Extensions of this inequality are also proved for regions in the spacetime which are not necessarily black hole boundaries.Comment: 21 pages, 2 figure

From a certain point of view: sensory phenomenological envisionings of running space and place

The precise ways in which we go about the mundane, repetitive, social actions of everyday life are central concerns of ethnographers and theorists working within the traditions of the sociology of the mundane and sociological phenomenology. In this article, we utilize insights derived from sociological phenomenology and the newly developing field of sensory sociology to investigate a particular, mundane, and embodied social practice, that of training for distance running in specific places: our favored running routes. For, despite a growing body of ethnographic studies of particular sports, little analytic attention has been devoted to the actual, concrete practices of “doing” or “producing” sporting activity, particularly from a sensory ethnographic perspective. Drawing upon data from a 2-year joint autoethnographic research project, here we explore the visual dimension, focusing upon three key themes in relation to our runners’ visualization of, respectively, (1) hazardous places, (2) performance places, (3) the time–space–place nexus

Lifting the Dusty Veil II: A Large-Scale Study of the Galactic Infrared Extinction Law

We combine near-infrared (2MASS) and mid-infrared (Spitzer-IRAC) photometry to characterize the IR extinction law (1.2-8 microns) over nearly 150 degrees of contiguous Milky Way midplane longitude. The relative extinctions in 5 passbands across these wavelength and longitude ranges are derived by calculating color excess ratios for G and K giant red clump stars in contiguous midplane regions and deriving the wavelength dependence of extinction in each one. Strong, monotonic variations in the extinction law shape are found as a function of angle from the Galactic center, symmetric on either side of it. These longitudinal variations persist even when dense interstellar regions, known a priori to have a shallower extinction curve, are removed. The increasingly steep extinction curves towards the outer Galaxy indicate a steady decrease in the absolute-to-selective extinction ratio (R_V) and in the mean dust grain size at greater Galactocentric angles. We note an increasing strength of the 8 micron extinction inflection at high Galactocentric angles and, using theoretical dust models, show that this behavior is consistent with the trend in R_V. Along several lines of sight where the solution is most feasible, A_lambda/A_Ks as a function of Galactic radius is estimated and shown to have a Galactic radial dependence. Our analyses suggest that the observed relationship between extinction curve shape and Galactic longitude is due to an intrinsic dependence of the extinction law on Galactocentric radius.Comment: Accepted to Ap